Researchers Distinguish Remyelinated Brain Lesions Via MRI

An MRI technique called quantitative susceptibility mapping (QSM) can be used to accurately identify remyelinated brain lesions in people with multiple sclerosis (MS), a research team has discovered.

Remyelinated lesions are those in which the myelin sheath — the protective coating around nerve fibers that is progressively lost in MS — has been repaired.

These study findings suggest that QSM data may represent a new biomarker to help develop and assess the efficacy of potential remyelinating treatments in clinical trials, the researchers noted.

The study, “A new advanced MRI biomarker for remyelinated lesions in Multiple Sclerosis,” was published in the journal Annals of Neurology.

In MS, the immune system launches an inflammatory attack that causes damage to myelin, ultimately resulting in demyelination, or myelin loss, in the brain and spinal cord. Areas of inflammation and resultant demyelination are visible on MRI scans as lesions.

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While myelin repair is a natural process upon demyelination, it is typically very inefficient in people with MS. Myelination also is difficult to monitor with current imaging techniques.

QSM, an MRI technique sensitive to both iron accumulation and myelin content in the brain, has been used to identify paramagnetic rim lesions (PRLs), which are regions of chronic inflammation and myelin damage that are surrounded by a “rim” of iron-laden immune cells, like microglia and macrophages.

Whether this technique can be used to accurately distinguish other types of MS lesions, particularly those presenting myelin repair, remains unclear.

To address this, an international team of scientists conducted analyses of MRI data for 1,621 lesions in 115 people with MS — 76 with active relapsing-remitting disease and 39 with inactive progressive MS (PMS). The analysis also included MRI data from 76 people without MS.

They classified MS lesions according to their visual intensity compared to the surrounding tissue on QSM maps: isointense (similar intensity, 29.4%); hypointense (lower intensity, 4.3%); hyperintense lesions (higher intensity, 52.2%), lesions with hypointense rim (1.2%); and lesions with hypertense rim, which are the PRLs (13%).

There was no difference in the frequency of QSM lesion types between RRMS and PMS patients.

The team then evaluated the myelin and nerve fiber content of each lesion type using the myelin water fraction (MWF) and neurite density index (NDI). MWF estimates myelin content based on the amount of water, while NDI measures how dense nerve fibers are in a region.

Results showed that PRLs were associated with the lowest MWF and NDI values, which is consistent with these lesions representing areas of ongoing inflammation that causes chronic demyelination. By contrast, isointense and hypointense brain lesions tended to have high MWF and NDI values, indicating higher myelin content — presumably due to remyelination.

“We present new evidence indicating that QSM lesion types differ substantially in their myelin and axon content, as measured by surrogate imaging measures such as MWF and NDI,” the researchers wrote.

The scientists then tracked MWF changes over time in 40 patients followed for two years. Of 325 lesions followed over time, 18 were isointense or hypointense lesions.

While MWF values remained largely stable in eight of these lesions over the two years (average increase of 3.6%), the other 10 initially were hyperintense lesions at study’s start and showed an average increase of 33.6% in MWF — suggesting remyelination in these regions.

To further investigate the ability of QSM to accurately identify the different types of lesions, the team compared data from QSM with that of tissue analysis in the brains of three deceased MS patients.

Based on tissue analyses, there were nine remyelinated lesions in these brains. Eight of these nine lesions had appeared as isointense or hypointense on MRI scans. The lone outlier, an hyperintense lesion, “was characterized by iron-rich macrophages/activated microglia and incomplete remyelination,” the researchers wrote.

Still, the QSM accurately identified fully remyelinated areas as isointense/hypointense with a sensitivity of 88.9% (true-positive rate) and a specificity of 100% (true-negative rate).

These findings suggest that “iso and hypointensity in QSM indicates complete focal remyelination with no active microglia or macrophages,” the researchers wrote.

QSM also accurately identified chronic inactive lesions (which no longer show signs of active inflammation) as hyperintense (sensitivity of 71.4%; specificity of 92%) and chronic active lesions as PRLs (sensitivity of 92.9%, specificity of 86.4%).

“We identified a new QSM lesion type, hypointense QSM lesions, which showed … the highest myelin and axon content compared to other QSM lesion types, suggesting that they may represent remyelinated plaques,” the researchers concluded.

These findings “provide the first evidence that it is possible to distinguish chronic MS lesions in a clinical setting,” the researchers wrote.

They also highlight that “QSM provides highly sensitive and specific biomarkers of completed remyelination,” which may help to develop and measure the efficacy of potential remyelinating therapies in clinical trials, the team concluded.